Abstract
Autosomal dominant nocturnal frontal lobe epilepsy is a familial partial epilepsy syndrome and the first human idiopathic epilepsy known to be related to specific gene defects. Clinically available molecular genetic testing reveals mutations in three genes, CHRNA4, CHRNB2 and CHRNA2. Mutations in CHRNA4 have been found in families from different countries; the Ser280Phe in an Australian, Spanish, Norwegian and Scottish families, and the Ser284Leu in a Japanese, Korean, Polish and Lebanese families. Clear evidence for founder effect was not reported among them, including a haplotype study carried out on the Australian and Norwegian families. Japanese and Koreans, because of their geographical closeness and historical interactions, show greater genetic similarities than do the populations of other countries where the mutation is found. Haplotype analysis in the two previously reported families showed, however, independent occurrence of the Ser284Leu mutation. The affected nucleotide was highly conserved and associated with a CpG hypermutable site, while other CHRNA4 mutations were not in mutation hot spots. Association with a CpG site accounts for independent occurrence of the Ser284Leu mutation.
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Acknowledgements
We thank the members of the family for their cooperation in this study and Akiyo Hamachi and Minako Yonetani for technical assistance. This work was supported in part by Grant-in-Aid for Scientific Research (A) 21249062; Japan Society for the Promotion of Science(JSPS); ‘High-Tech Research Center’ Project for Private Universities—matching fund subsidy from the Ministry of Education, Culture, Sports, Science and Technology; 2006–2010—‘The Research Center for the Molecular Pathomechanisms of Epilepsy, Fukuoka University’; research Grants (21B-5) for Nervous and Mental Disorder from the Ministry of Health, Labor and Welfare; Health and Labor Science Research Grant (21210301); KB220001 from the Ministry of Health, Labor and Welfare; Adaptable and Seamless Technology Transfer Program through target-driven R&D (A-STEP) exploratory research; Japan Science and Technology Agency (JSP); International Research Fund for Subsidy of Kyushu University School of Medicine Alumini; The Japan Epilepsy Research Foundation (H22-005); and research Grant from Keimyung University, Korea.
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Hwang, SK., Makita, Y., Kurahashi, H. et al. Autosomal dominant nocturnal frontal lobe epilepsy: a genotypic comparative study of Japanese and Korean families carrying the CHRNA4 Ser284Leu mutation. J Hum Genet 56, 609–612 (2011). https://doi.org/10.1038/jhg.2011.69
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DOI: https://doi.org/10.1038/jhg.2011.69
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